This invention relates to an improved device for automated pipetting of small volumes of liquid.
Today there is a great demand for high-throughput biological and chemical synthesis, analysis and sample processing. In chemical and biological laboratories, sample transfer from a source plate to a target plate (or piece of lab ware) is a fundamental task. Typically a pipette or pipetter system is used to (i) collect a desired sample from the source piece of lab ware which holds the sample in one array format, and (ii) deliver/dispense the collected sample to the target piece of lab ware in the same or another array format. During the transfer of samples, it is extremely important to dispense and aspirate precise volume samples and to avoid their cross-contamination.
One pipetting device which addresses the need for high-throughput Hydra(copyright) Microdispenser (Robbins Scientific, Inc., Sunnyvale, Calif.) uses several syringes positioned together in a holder. The syringes utilized are made of high quality borosilicate glass, the inner chambers of the barrels are precision-machined and highly polished to ensure leak-free performance. The Teflon(copyright) tips used on the stainless steel plungers are ribbed to prevent liquid from leaking around the tip under pressure. Each needle of the pipetting apparatus is permanently fixed into a Teflon seal at the end of the syringe barrel. An array of these syringes requires large actuation forces because of the friction in the seals. The cost of each such syringe is also high due to the precise machining of the glass. Moreover, the use of movable seals on a syringe can lead to inconsistency in pressure on the samples result in imprecise volumes of sample.
Another pipetter system for pipetting in parallel is disclosed in U.S. Pat. No. 5,541,889. This system has an actuator which operates an upper plate assembly which holds a plurality of metal rods, such that all the rods are moved together along parallel longitudinal axes in respective tubes. It utilizes less actuation force than the previously disclosed invention by having the plurality of metal rods come in direct contact with the sample fluids for aspirating and dispersing. The actuator raises the upper plate assembly and the plurality of rods simultaneously traverse the length of their respective tubes for aspiration. For dispersion of the samples, the actuator is lowered very rapidly and stopped abruptly and in turn, the upper plate assembly is lowered very rapidly and stopped abruptly. This imparts a high velocity to the collected sample fluid within the tubes and the samples use their own inertia to exit the distal end of the tubes. The liquid samples involved in biological and chemical synthesis, analysis and sample processing are often corrosive could lead to the destruction of the metal rod design disclosed.
What is needed is an improved pipetting apparatus that is durable and capable of efficiently dispensing and aspirating multiple precise volumes of samples without the cross-contamination of samples.
The present invention addresses the problems of efficiency, purity, and precision of samples.
In a first embodiment, a micropipetter includes a plurality of hollow needles to deliver fluid, said needles being anchored in a sample block; a needle guide assembly comprising a plurality of needle guide shafts and compression springs attached at one end to the sample block and at the other end to a needle guide plate, each spring surrounding a needle guide shaft, and the needle guide plate guiding the spacing of the needles; a sample block having a plurality of hollow spaces, each of which connect with the hollow needle; a displacement volume block having a plurality of hollow spaces, each being occupied by a piston pin, each piston pin being sealed with a stationary seal assembly; a stationary sheet seal located between the sample block and the displacement volume block, the sheet seal having a plurality of holes corresponding to and separating the spaces in the sample block and the displacement volume block, such that precise volume displacement is provided; a seal constraint plate located above the displacement volume block, the seal constraint plate being positioned to hold in place an airtight, low-friction seal assembly around each of the piston pins; the piston pins being attached to a piston pin plate; and motive means for moving the pistons vertically and thereby alternately aspirating fluid into the needles and dispensing fluid from the needles.
In a further embodiment, the seal assembly has at least one sleeve which is in contact with the piston pin, at least one O-ring. The sleeve can be Teflon. The motive means is at least one motor having at least one lead-screw drive which goes through the core of the motor, the lead-screw drive being attached to an armature, such that actuating the motor causes the lead-screw drive to pull up or lower the rest of the micropipetter. The micropipetter further has at least one set of crossbars, each crossbar being attached to the constraint plate and the piston pin plate, thereby increasing stability of the micropipetter and aiding in precise movement. The hollow needles can number 1, 8, 16, 24, 96, 384 or 1536. The motive means can be controlled by an on-board microprocessor.
In yet another embodiment, the micropipetter can be provided with a counter-balance to aid in hand-held use.
In yet another embodiment, the disclosed micropipetter is incorporated into a robotic workstation.